Cellular and clinical report of new Griscelli syndrome type III cases

• DOI: 10.1111/j.1755-148x.2011.00901.x
• Publication Date: 2011-09-01T01:59:19Z
• Authors: Wendy Westbroek; Aharon Klar; Andrew R. Cullinane; Shira G. Ziegler; Haggit Hurvitz; Ashraf Ganem; Kirkland Wilson; Heidi Dorward; Marjan Huizing; Haled Tamimi; Igor Vainshtein; Yackov Berkun; Moran Lavie; William A. Gahl; Yair Anikster
• Keywords: Melanosome; Melanocyte; Pigmentation disorder

The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes subsequent transfer to keratinocytes. Mutations any one member this cause three forms Griscelli syndrome (GS), each with distinct clinical features but a similar cellular phenotype. To date, only case GS type III (GSIII), caused by mutations Melanophilin (MLPH) gene, has been reported. Here, we report seven new cases GSIII Arab pedigrees. All affected individuals carried homozygous missense mutation (c.102C>T; p.R35W), located conserved Slp homology domain MLPH, and had hypomelanosis skin hair. We first studies on melanocytes, which demonstrated that MLPH(R35W) causes perinuclear aggregation typical GS. Additionally, co-immunoprecipitation assays showed lost its interaction RAB27A, indicating pathogenicity R35W mutation.